Project Summary: This project aims to demonstrate the feasibility of non-invasive optical measurements of the dynamic time courses of hemodynamic and metabolic changes associated with brain activation, systemic changes in mean arterial pressure, and spontaneous hemodynamic oscillations in human subjects. Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique that measures the cerebral concentrations of oxy-hemoglobin (O) and deoxy-hemoglobin (D). The biological origin of O and D changes includes hemodynamic changes described by cerebral blood volume (CBV) and cerebral blood flow (CBF), and metabolic changes described by the cerebral metabolic rate of oxygen (CMRO2). We have recently introduced a novel hemodynamic model that translates dynamic changes in CBV, CBF, and CMRO2 into O and D changes that are measured by fNIRS. It is a multi-compartment model that takes into account the dynamic effects associated with capillary and venous blood transit times. Because our model predicts that fNIRS signals depend on the difference of CBF and CMRO2 changes, we propose to complement fNIRS with measurements of CBF with diffuse correlation spectroscopy (DCS), which is also a non-invasive optical technique. We propose to perform the analysis of concurrent and co-localized fNIRS and DCS data with our new hemodynamic model to generate dynamic traces of CBV, CBF, and CMRO2 that describe hemodynamic and metabolic transients and fluctuations. This is an innovative approach with respect to current methods in the fields of functional MRI and optical imaging that are commonly based on steady state models, which are intrinsically inadequate for the study of transient conditions. We also hypothesize that a universal dynamic relationship between optically measured CBV and CBF can be identified to allow for dynamic measurements of CBV, CBF, and CMRO2 with stand-alone fNIRS. We will perform human studies to demonstrate the feasibility of the proposed methods to characterize brain activation, controlled perturbations to the mean arterial pressure, and spontaneous hemodynamic oscillations at rest. This project will result in the development of a powerful optical tool for the functional study of the human brain to characterize brain activation conditions and resting state functional connectivity. Such a tool can significantly impact functional neuroimaging research and find clinical applications in the diagnosis and assessment of neurovascular disorders.